DESCRIPTION: (Applicant's Abstract) Marijuana is the most commonly used illegal drug, and it is frequently used by adolescents during a time when substantive developmental changes are taking place in the brain. Therefore, its effects on brain structure and function are of considerable importance. It is well established that acute administration of marijuana has significant behavioral and physiological effects. However, data to support chronic and/or residual changes are more elusive. We have collected MRI and CBF data on 57 marijuana users. MRI scans were used to determine brain volume measurements. These data indicate significant differences in gray matter volume related to the age when marijuana was first used. Early users have significantly smaller gray matter volume compared to later users. In the proposed project, we will study two groups of marijuana smokers, those who started using marijuana before age 15 and those who started smoking after age 18, and compare them to drug-na&iuml;ve normal controls. Exclusion of drug use in controls is difficult but essential in testing the hypotheses. We will compare subjects on volume estimates of gray and white matter in cortical and subcortical structures obtained with MRI, neuropsychological testing and measurement of cerebral blood flow obtained with Positron Emission Tomography (PET), while performing an activation task.